Project Summary/Abstract Candidate: The Candidate is currently an Assistant Professor in Orthopaedic Surgery at Washington University in St. Louis. He holds a Ph.D. in Biomedical Engineering and has previously completed a NIH NRSA F32 Postdoctoral Fellowship examining the role of Matrix Metalloprotease-13 in the osteocyte-mediated bone homeostasis. His long-term goal is to develop successful research enterprise as a translational musculoskeletal researcher to investigate the risk factors (such as diabetes and other metabolic factors) and the disease mechanisms of skeletal disorders. This proposed project would provide to the candidate an improved understanding of low back pain, as well as the ability to design, conduct, and collaborate on human- based studies. The completion of the project is expected to generate an exciting and innovative research direction to enable the Candidate to carve out an independent niche and position him to secure sustained extramural funding. Mentor and Advisory Committee: The mentoring committee is lead by primary mentor, Dr. Linda Van Dillen, P.T., Ph.D., a clinician-scientist at Washington University in St Louis. She is an international leader in the measurement and classification of people with low back pain. Other mentors include Dr. Sam Ward, P.T., Ph.D., one of the pioneering experts in the world in the use of Open, Upright Magnetic Resonance Imaging. Dr. Mathew Silva, Ph.D., Julia & Walter Peterson Professor in Orthopaedics, has extensive experience in the imaging of skeletal tissues and biomechanics, will advise on image processing, research strategies, and career development. Dr. Lori Setton, Ph.D. Lucy & Stanley Lopata Distinguished Professor of Biomedical Engineering, will provide expertise in intervertebral disc mechanobiology and biomechanics, as well as career development and grant writing. The candidate has also assembled a team of consultant to lend expertise to the project: Dr. Munish Gupta, M.D. (Distinguished spine surgeon) for his insights in clinical presentations of low back pain; Dr. Aseem Sharma, M.D. (neuroradiologist) for his insights in the degenerative classification of the spinal structures; and Dr. Kishan Yalavarthi, M.D. (radiologist and medical director for the Open Upright MRI Center of Missouri) who will provide support for sequence optimization and image interpretation. Environment: The candidate has been provided at least 1,500 sq ft of laboratory space (4,000 sq ft of shared space between the Dr. Silva and Dr. Thomopoulos lab groups) in the Musculoskeletal Research Center (MRC - NIH P30 AR057235) at Washington University in St Louis. He has access to the Musculoskeletal Structure and Strength Core (where Dr. Tang also serves as the Associate Director); In Situ Molecular Analysis core; and Mouse Genetics core. There are 14 musculoskeletal research labs adjacent to the candidate's space on the same floor utilizing an open space format, which enable substantial resource and substantial resource sharing. Dr. Van Dillen directs the Musculoskeletal Analysis Lab which is in close proximity to Dr. Tang's laboratory and office. The lab is used for testing of subjects with instrumented measures. The laboratory also includes a private examination room. Here people complete self-report measures, participate in interviews and testing using clinical measures, such as our standardized clinical examination, and change their clothes in preparation for instrumented testing. The laboratory is equipped with a 3-dimensional, video-based Vicon motion capture system with 8, MX-T40 2000 Hz infrared cameras. Dr. Van Dillen has a commitment from 4 clinical facilities for subject recruitment and all are located in close proximity to the 4444 Forest Park Building where examination and laboratory testing will take place. All 4 of the sites are a part of the Washington University School of Medicine and affiliated with the Barnes-Jewish Hospital and Washington University School of Medicine outpatient clinics. Training Plan: The training plan includes practical training in the design and execution of human-based studies as instructed by Dr. Van Dillen. Didactic training includes course work from Clinical Research Training Center and includes courses in ethics, epidemiology, and outcomes research. Washington University provides an academically rich environment for seminars and collaborative interactions. Finally, regular meetings with mentors Drs. Silva, Setton, and Ward will guide career development and discuss findings. Research: Dr. Tang will examine the loaded spine in homogenous subgroups of people with non-specific low back pain, classified using clinical examination data and kinematic metrics. Subsequently, these individuals will be imaged using the Open, Upright MRI with a T2-weighted sequence to examine changes in the spine during loaded and non-loaded states. The proposed studies are expected to identify the deformational changes of the loaded spine and how they are altered with LBP. The long-term objective is to define the multiscale clinical tools that relate clinical examination findings and the associated pathophysiology in LBP; and using these findings to guide clinical and rehabilitation strategies. Institutional Commitment to the Candidate: The Candidate holds a tenure-track faculty position in the Department of Orthopaedics at Washington University in St Louis, which has provided a newly renovated laboratory, start-up package, and support for staff/postdocs.